Project Summary Here we propose to develop and integrate a suite of experimental and computational tools to measure the visual response and network properties of a large population of neurons in the mouse superior colliculus (SC), to determine how these properties change during locomotion, and the contribution of cortical and specific retinal inputs to these properties. The mouse SC is a subcortical area that integrates vision with touch and hearing to initiate orienting movements of the eyes and head, and is an attractive model to study how specific circuits form during development. Our development of high-density, high-channel count silicon probes to record neural activity has several significant advantages compared to alternative methods: (1) high efficiency for recording neuron spatial and temporal visual response properties; (2) the ability to rapidly study the topological/functional organization in a large neuron population over a wide field of view in a uniform way in a single animal; (3) the possibility to study correlated activity and connectivity among neurons as well as network rhythms; (4) the ability to ascertain differences in visual responses associated with behavioral state such as locomotion. Experiments proposed in Aim 1 will measure the functional and topological properties of visually- responsive neurons in the SC of mice that are awake and head-fixed on a freely-floating Styrofoam ball used as a spherical treadmill. For each neuron, the spatial receptive field (RF), the temporal filtering spike-triggered average (STA), direction and orientation selectivity, and the non-linearity of spatial summation will be determined and correlated with its location in the SC and correlated with locomotion. Aim 2 will apply the recording and data analysis tools developed in Aim 1 toward understanding the changes in circuitry in mutant mice that lack cortical inputs to the SC or lack On-Off direction selecive retinal ganglion cells (DS RGCs). This will allow us to determine the contribution of the cortex and DS RGCs toward the receptive field properties of SC neurons. Upon completion, a comprehensive classification of SC neurons, their topological organization, and their coding properties will be in hand. We will then take advantage of the ever-expanding availability of genetic tools (including optogenetics) that alter visual function, and mouse models of complex neurological disease that have altered activity patterns such as autism and schizophrenia. These same techniques will be useful to understand the circuitry of brain areas of animals with more complex visual systems and brain circuitry such as cat, ferret, and non-human primates.